dactinomycin / Generic mfg. - LARVOL DELTA

HOXA9/METTL3/BMI1 axis is required for promoting anthracycline resistance in acute myeloid leukemia cells by modulating BMI1 expression through mRNA m6A modification (ASH 2025) - "The traditional "3+7" inductionregimen with anthracycline and cytarabine remains a standard therapy, but 30%-40% of patientsdevelop drug resistance to anthracyclines, leading to relapse...MeRIP-qPCR validatedm6A-modified mRNAs and actinomycin D assays tested RNA stability...Conversely, METTL3 overexpression in sensitive cellsenhanced m6A modification, promoted proliferation, suppressed apoptosis, and augmented doxorubicinresistance...Furthermore, anthracycline exposure leads toa further increase in chromatin accessibility at the METTL3 promoter in resistant cells, suggestingdynamic epigenetic modulation of this key m6A regulator during drug resistance. Our studydemonstrated that The HOXA9/METTL3/BMI1 axis promotes anthracycline resistance in acute myeloidleukemia through mRNA m6A modification and suggested the therapeutic potential of targeting theMETTL3/BMI1 axis in the treatment of anthracycline-resistant AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BMI1 • HOXA9 • METTL3

Methionine promotes glycolysis and tumor progression in multiple myeloma by enhancing POU2AF1 expression via m⁶A modification (ASH 2025) - "MeRIP-qPCR was employed to verify m6A modification changesin POU2AF1, and an actinomycin D assay was conducted to evaluate its impact on the stability ofPOU2AF1 mRNA... MM exhibits a pronounced dependence on methionine, with enhanced methionineuptake through the upregulation of the transporters SLC6A18 and SLC38A5. Methionine promotes MMglycolysis and tumor progression by facilitating the m6A modification of POU2AF1, which increases itsstability and expression. These findings suggest that targeting methionine metabolism represents apromising therapeutic strategy for MM."

Hematological Malignancies • Multiple Myeloma • Oncology • POU2AF1 • SLC38A5

Discovery of an undocumented pattern of intron retention that is abundant in healthy B-cells and circumvented in Waldenstrom's macroglobulinemia impacting genes driving cellular growth and survival (ASH 2025) - "To test if RNAdegradation could explain the disappearance of these retentions within two-hours, cells were exposed tothe transcriptional and splicing inhibitor actinomycin D. We observed the NFKB2 retentions were quitestable relative to the SGK1 quick decay control and were still present at the 3-hour mark long after theyhad disappeared in our DMSO controls... Undocumented intron retentions that impact translation of genes important to WM growthand survival including NFKB2 and BTK are highly prevalent in HD B-cells but absent in WM LPCs. Ourstudies show that NFKB2, a key mediator of non-canonical NFKB pro-survival signaling, is primarilyproduced with retained introns that prevent their translation and are post transcriptionally spliced in thecytoplasm of HD B-cells. Our findings provide novel insights into the role of splicing and translation of keypro-survival proteins in WM pathogenesis."

Clinical • IO biomarker • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CD27 • IRAK4 • MYD88 • NFKB2 • SDC1

PHF19 inhibition increases IMiDs sensitivity by epigenetically regulating IRF4 and MYC in multiple myeloma (ASH 2025) - "Integrated RNA-seq/ATAC-seq analysis identified 391overlapping genes enriched in cell cycle regulation, including IRF4 and MYC, suggesting that PHF19sustains their expression by modulating transcriptional accessibility.Additionally, mRNA stability assays using actinomycin D revealed that IRF4 and MYC transcripts weredestabilized in PHF19-KD cells, implicating PHF19 in post-transcriptional regulation.Our group previously linked PHF19 to resistance to proteasome inhibitors (PIs) and anti-CD38monoclonal antibodies...Strikingly, PHF19 depletion sensitized MM cells to IMiDs.Mechanistically, IMiDs treatment further suppressed IRF4 and MYC in PHF19-KD cells, whereas theirlevels remained stable in controls.PHF19 is overexpressed in immunotherapy non-responders and drives resistance by sustaining IRF4/MYCexpression through dual epigenetic (chromatin remodeling) and post-transcriptional (mRNA stabilization)mechanisms. Targeting the PHF19-IRF4-MYC axis enhances IMiD sensitivity,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • IRF4 • MYC • SDC1

Hypomethylating agents or chemotherapy in combination with venetoclax and gilteritinib for FLT3-mutated Acute Myeloid Leukemia (ASH 2025) - "Three different remission induction regimens were used: AzaVenGilt (azacitidine 75 mg/m2 (days 1-7) +venetoclax 400 mg (days 1-14) + gilteritinib 80/120 mg (days 1-14)), DecVenGilt (decitabine 20 mg/m2(days 1-5) + venetoclax 400 mg (days 1-14) + gilteritinib 80/120 mg (days 1-14)), or ACTIVE+Gilt(actinomycin D 12.5 mcg/kg (days 1-3) + cytarabine 20 mg/m2 (days 1-10) + venetoclax 600 mg +gilteritinib 80/120 mg (days 4-18). The 12 and 24-month OS probabilities were 59 % and 52 % for all patients,respectively. The 12 and 24-month RFS probabilities were 49.5 % and 41.8 % for all patients, respectively.Day 30 and day 60 mortality rates were 3 % (1/39) and 10 % (4/39), respectively.CONCLUSIONSFrontline triplets with HMA, venetoclax, and gilteritinib, as well as the salvage quadruplet withactinomycin D, cytarabine, venetoclax, and gilteritinib, demonstrate high antileukemic efficacy and amanageable safety profile for FLT3-m AML patients in the clinical practice setting."

Combination therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • FLT3

RBM7 suppresses mitochondrial dysfunction and ferroptosis by destabilizing FBXL16 mRNA to enhance Temozolomide resistance in glioblastoma. (PubMed, Mol Genet Genomics) - "An actinomycin D assay analyzed FBXL16 mRNA stability. RBM7 promotes TMZ resistance by suppressing mitochondrial dysfunction and ferroptosis through destabilization of FBXL16. Targeting the RBM7-FBXL16 axis may represent a novel strategy to overcome GBM chemoresistance."

Journal • Brain Cancer • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor • ATF4 • FBXL16 • TCF4

The Pharmacological Atlas of Meningiomas (SNO 2025) - "The top five drugs with the lowest IC50 values were romidepsin, dactinomycin, carfilzomib, plicamycin, and omacetaxine, with median values of 10, 31, 145, 303, and 400 nM, respectively. Considering the ratio of peak serum concentration (Cmax) to IC50 as a potential predictor of treatment efficacy (>1), the HDAC inhibitors belinostat (74.5), romidepsin (69.7), along with the proteasome inhibitor carfilzomib (34.6), and the anthracyclines epirubicin (2.6), and doxorubicin (1.8), and the PI3K inhibitor idelalisib (1.6) are the most promising drug candidates for further evaluation. This study offers the first comprehensive insight into the pharmacological landscape of meningiomas, providing a crucial foundation for future clinical trials aimed at developing systemic treatments for aggressive meningiomas."

Brain Cancer • Meningioma • Solid Tumor

Circ_0001741 regulates proliferation and invasion in ESCC via the miR-194-5p/E2F3 axis. (PubMed, World J Surg Oncol) - "Our findings establish that circ_0001741 drives ESCC progression by modulating the miR-194-5p/E2F3 axis, underscoring its therapeutic potential for ESCC treatment."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma • E2F3 • MIR194

Investigating the prognostic potential of PTPN11 gene in papillary thyroid carcinoma: A comprehensive study of bulk and single cell transcriptome. (PubMed, Medicine (Baltimore)) - "It exhibited strong binding affinities with VX-11e, irinotecan, and dactinomycin. Endothelial cells were identified as key cells; the occurrence of PTC reduced their quantity and affected the frequency/intensity of their interactions with mast cells. In conclusion, PTPN11 holds promise as a prognostic marker for PTC and is of great value for clinical management."

Biomarker • Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • DACT2 • MMP8 • NCAM1 • PTPN11

Circular RNA collagen type V alpha 1 exerts a carcinogenic role in renal cell carcinoma via modulating microRNA-3940-3p/Karyopherin α2 axis. (PubMed, J Physiol Pharmacol) - "The characteristics of circCOL5A1 were verified by RNase R and actinomycin D experiments, and its subcellular localization was analyzed by PARIS kit...CircCOL5A1 promoted cell proliferation, migration, invasion, EMT and glycolysis by cytoplasmic adsorption of miR-3940-3p and up-regulation of KPNA2 in RCC. CircCOL5A1 is anticipated to be a promising molecular target for diagnosing and treating RCC."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CDH1 • CDH2 • COL5A1 • KPNA2 • VIM

Optimized Quantitative Assessment of Enhancer RNA Stability in Mouse Embryonic Stem Cells. (PubMed, J Vis Exp) - "Transcription is inhibited using Actinomycin D, and total RNA is collected at multiple defined time points...The protocol reveals that eRNAs in mESCs exhibit rapid turnover, with a half-life of approximately 2-3 min. This methodology provides a robust and reproducible framework for studying eRNA stability, offering insight into enhancer activity and RNA dynamics in pluripotent stem cell contexts."

Journal • Preclinical

Lactylation-driven NSUN2-mediated RNA m5C modification promotes perineural invasion in pancreatic cancer. (PubMed, Theranostics) - "Mechanistic interrogation combined NSUN2 knockout, CRISPR knock-in mutants at K692 (K692R/E), co-immunoprecipitation, RIP-seq, MeRIP-qPCR, and actinomycin-D chase to test mRNA binding, m5C modification, and stability of CDCP1/STC1... This study identifies lactate-driven NSUN2 K692 lactylation as a key driver of perineural invasion in PDAC. We define a lactate-NSUN2-m5C-CDCP1/STC1 axis that links metabolic stress-induced lysine lactylation to mRNA methylation-dependent stabilization of pro-invasive transcripts, highlighting actionable therapeutic targets to restrain neural invasion and improve patient outcomes."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Targeted Protein Degradation • CDCP1 • STC1

GAMMA: Results from a Phase II Study for Relapsed Germ Cell Tumors using an Oxaliplatin-Based Treatment Regimen. (PubMed, Clin Genitourin Cancer) - "The GAMMA regimen demonstrates encouraging antitumor activity in relapsed GCT, despite recruiting a cohort of patients with predominantly poor risk disease."

Journal • P2 data • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer

Advanced Wilms Tumor in a Middle-Aged Adult: A Case Report. (PubMed, Clin Case Rep) - "She was discussed in a multidisciplinary team, and a consensual decision was made to be given palliative chemotherapy with a combination of vincristine, dactinomycin, doxorubicin, and cyclophosphamide after optimization. This case report highlights the rarity of Wilms tumor in adults, especially in middle age, and emphasizes the importance of considering it in the differential diagnosis of renal masses."

Journal • Embryonal Tumor • Genito-urinary Cancer • Kidney Cancer • Nephrology • Oncology • Pain • Pediatrics • Renal Cell Carcinoma • Solid Tumor • Wilms Tumor

PROGNOSTIC RELEVANCE OF CYCLOPHOSPHAMIDE DOSE FOR HIGH-RISK RHABDOMYOSARCOMA IN ADULT PATIENTS TREATED WITH VAC THERAPY (CTOS 2025) - "Treatment strategies frequently follow pediatric protocols, such as vincristine, actinomycin D, and cyclophosphamide (VAC) regimen, despite concerns regarding toxicity in adults. In this retrospective analysis, a high starting dose of cyclophosphamide did not result in a statistically significant survival difference compared to a low-dose regimen in adult patients with high-risk RMS."

Clinical • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FOXO1

Evolutionary Therapy for Rhabdomyosarcoma (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Recruiting ➔ Active, not recruiting | N=28 ➔ 12

Enrollment change • Enrollment closed • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FOXO1

Mining Actinomycetes' Metabolomes and Genomes for Anti-Phytophthora infestans Compounds. (PubMed, Microb Biotechnol) - "Our analysis putatively identified over 75 compounds with potential activity against P. infestans, including borrelidin, actinomycin D, antimycin A, macbecin I, myriocin and ikarugamycin. Our study shows that leveraging multi-omics analysis of phylogenetically related strains with differential activity is a promising strategy which, combined with a relatively high throughput metabolite extraction method, advanced mass spectrometry and cutting-edge tools for bacterial metabolite annotation and prediction, allowed a straightforward selection of interesting candidate compounds for the biological control of an important plant pathogen such as P. infestans. The methodology outlined here offers broader applicability for identifying bioactive compounds underlying any phenotype of interest, provided this phenotype varies in phylogenetically closely related strains."

Journal

DDX3X promotes ILF3 stability to accelerate neuroblastoma progression via M2 macrophage polarization. (PubMed, Brain Res) - "Actinomycin D treatment combined with RT-qPCR was used to assess ILF3 mRNA stability...In vivo, DDX3X inhibitor, RK-33, markedly inhibited NB tumor growth and metastasis and enhanced M1 macrophage polarization, which was partially reversed by ILF3 overexpression. DDX3X promotes NB progression by stabilizing ILF3 mRNA, thereby facilitating M2 macrophage polarization."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • DDX3X • IL3

The role of CSTF2 in gastric cancer: implications for therapy. (PubMed, Eur J Med Res) - "CSTF2 promotes gastric cancer progression by post-transcriptionally stabilizing TGM2 mRNA, and its overexpression is closely related to poor prognosis. The elucidated CSTF2-TGM2 regulatory axis may offer a promising and innovative therapeutic target for gastric carcinoma treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • TGM2

A novel positive-feedback loop between CEBPA and NAT10 promotes non-small cell lung cancer progression. (PubMed, Cytotechnology) - "Additionally, mRNA stability was evaluated using actinomycin D assay...NAT10 catalyzed ac4C acetylation on CEBPA mRNA, enhancing its stability and increasing CEBPA protein expression, thereby promoting the malignant progression of NSCLC. The identification of this feedback loop provides a preclinical rationale for developing NSCLC therapeutic strategies targeting NAT10 or CEBPA."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEBPA • NAT10

FTO-mediated m6A demethylation of BECN1 mRNA promotes hepatic steatosis by impairing autophagy. (PubMed, BMC Immunol) - "Lipid levels were measured enzymatically; autophagy markers were assessed by Western blot; m6A modification was evaluated via dot blot, MeRIP, and RIP assays; and RNA stability was determined using actinomycin D. In vivo, high-fat diet (HFD)-fed mice were established...In conclusion, FTO deficiency enhances BECN1 m6A methylation and mRNA stability, promoting autophagy and ameliorating lipid accumulation. These findings identify FTO as a potential therapeutic target for treating hyperlipidemia and related metabolic disorders."

Journal • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • BECN1 • FTO

Wilms Tumor 1-associated Protein Promotes Sepsis-induced Disseminated Intravascular Coagulation by Stabilizing Intercellular Adhesion Molecule 1 Via N6-methyladenosine Modification. (PubMed, Cardiovasc Drugs Ther) - "WTAP stabilizes ICAM1 mRNA via m6A modification, thereby increasing ICAM1 expression and enhancing TF activity in LPS-stimulated HUVECs. Knocking down WTAP in rats improves sepsis-induced DIC."

Journal • Infectious Disease • Nephrology • Oncology • Septic Shock • Solid Tumor • Wilms Tumor • ICAM1 • WT1 • WTAP

The Pharmacological Atlas of Meningiomas (WFNOS 2025) - "The top five drugs with the lowest IC50 values were romidepsin, dactinomycin, carfilzomib, plicamycin, and omacetaxine, with median values of 10, 31, 145, 303, and 400 nM, respectively. Considering the ratio of peak serum concentration (Cmax) to IC50 as a potential predictor of treatment efficacy (>1), the HDAC inhibitors belinostat (74.5), romidepsin (69.7), along with the proteasome inhibitor carfilzomib (34.6), and the anthracyclines epirubicin (2.6), and doxorubicin (1.8), and the PI3K inhibitor idelalisib (1.6) are the most promising drug candidates for further evaluation. This study offers the first comprehensive insight into the pharmacological landscape of meningiomas, providing a crucial foundation for future clinical trials aimed at developing systemic treatments for aggressive meningiomas."

Brain Cancer • Meningioma • Solid Tumor

CircPSMA4 as a novel circular RNA enhances the proliferation migration invasion and metabolism of bladder cancer cells through the miR-767-3p/HIF1A pathway. (PubMed, Sci Rep) - "The expression and in vitro functionality of circPSMA4 in T24 bladder cancer cell lines were analyzed using RNase R treatment, actinomycin D stability assay, nucleocytoplasmic separation, real-time quantitative PCR, Western blot, dual-luciferase reporter assay, cellular energy metabolism analysis, scratch assay, Transwell migration and invasion assay, CCK-8 proliferation assay, lactate and glucose uptake detection, and ATP production measurement...CircPSMA4 functions as a miR-767-3p sponge, regulating miR-767-3p to influence the expression of HIF1A, thereby promoting the proliferation, migration, invasion, and metabolic activities of bladder cancer cells, as well as tumor formation. CircPSMA4 facilitates the proliferation, migration, invasion, and metabolism of bladder cancer cells through the miR-767-3p/HIF1A pathway."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • HIF1A

Individualized Sequential Allogeneic Stem Cell Transplantation for Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Patients with Active Disease (ASH 2024) - "Five backbones were used for preconditioning : De-ACTIVE (Decitabine 20 mg/m2 on days 1-10, Actinomycin D 12.5 mcg/kg on days 1-3 + Cytarabine 20 mg/m2 on days 1-10, Venetoclax 600 mg/d on days 1-10), ACTIVE (Actinomycin D 12.5 mcg/kg + Cytarabine 20 mg/m2 + Venetoclax 600 mg/d), De-CAVE (Decitabine 20 mg/m2 + Cytarabine 20 mg/m2 + Venetoclax 600 mg/d), Ven + HMA (Venetoclax 400 mg/d + Decitabine 20 mg/m2 or Azacitidine 75 mg/m2) or Ven + LDAraC (Venetoclax 600 mg/d + Cytarabine 20 mg/m2)...Additional Gilteritinib, Trametinib, Dasatinib, Navitoclax, and Cladribine were used based on AML genomics and FAB classification...CONCLUSIONS Sequential alloSCT with Venetoclax-based low intensity preconditioning followed by conditioning and alloSCT demonstrates high antileukemic efficacy in difficult-to-treat R/R AML or HR-MDS patients with active disease in a real-world setting. However, the treatment was associated with high rates of severe infectious complications and notable..."

Clinical • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Transplantation • TP53